Previous studies have established XAF1 as a proapoptotic tumor suppressor that functions within a positive autoregulatory loop with TP53. 9Consistent with these findings, individuals who inherit the compound mutant haplotype (TP53 p.R337H; XAF1 p.E134∗) are at an increased risk for cancer in general, sarcomas, and multiple tumors compared with those carriers with only the p.R337H mutation.8 Here, XAF1 is linked to cancer.